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Posted 6/30/2012 6:35 PM (GMT 0)

My 57-yr old husband was diagnosed with advanced PC in October, following a  78 PSA finding during routine physical (he hadn't had a physical in a long time, but wasn't having any symptoms of anything). Clinical diagnosis was cT3, Gleason 8. Bone scan was clear but MRI showed extensive tumor, outside prostate and involving seminal vesicles and possibly bladder and rectum. Also 2 likely lymph nodes involved.

He has a great urologist--my husband wanted surgery and his urologist was willing to work with his more advanced case. He was put on Lupron for 3 months with purpose of shrinking the tumor to improve surgucal outcome. The 3 month check-up showed that the tumor was smaller, and rectum was clear (as DRE also proved) and urologist felt another 3 months would further improve things. So after 6 months on Lupron, he had robotic prostatectomy at the beginning of May.

The surgery was extensive, as the tumor was still large. Path report showed Gleason 8; tumor classified as T4 as it had involved the bladder neck; seminal vesicles involved, surgical margins at bladder base and urethra, as well as anterior and posterior apex. 2 lymph nodes involved. Because of the lymph nodes N1, my husband has been kept on Lupron.

The urologist/surgeon said after the surgery that the cancer had reached the bladder neck and had been a difficult resection. My husband asked if he "got it all" and he said yes, although I thought he sort of hesitated. He didn't mention any other surgical margins--the path report was mailed to us later.

My husband is not interested in reading these reports or otherwise reading PC studies etc. He feels that his dr is doing the best he can for him and he is mentally better off to trust that. I agree on his perspective, especially as the Lupron shots are affecting him emotionally and he doesn't need further triggers for depression. He knows I read the reports and do research and is interested in any positive information I find.

My questions relate to information from the pathology amd lab reports that is rather negative--not something I want to ask the urologist while with we are with him if he isn't bringing it up himself.

The biopsy report in October showed Gleason 4+4 involving 95% of right specimens, and 80% of left side, also Gleason 4+4. Clearly that isn't good. It also says that one right-side "block" had aneuploid DNA cells. 50% S-phase, which is "high," associated with larger tumor volume. The proliferation index Ki-67 (MIB-1) = 4.78%--it says this is a low value, but "high" starts at 5.00%.

The pathology report also reports aneuploid cells in one right block, and 4.34% proliferation--no S-phase reported.

I know aneuploid cells are a negative prognostic factor--but does anyone have experience in what these "details" suggest?

His pre-surgery PSA (only one since the original) was 1.8. Does anyone know how that stacks up after 6 months of Lupron? It's less than 90% but still significantly higher than "undetectable." He'll have a post-surgery reading in a month, 3 months after the surgery.

I appreciate any insights--I've been looking at these postings and people are helpful and informed.

Pilgrimess

Husband:

Age 57
First PSA 9/11 77.8
cGleason 8, 85% left, 90% right
cT3
6 mo lupron to shrink tumor
5/12 RP: pG8, pT4N1, sem ves pos, mult surg marg pos, 2 LN pos
pre-RP PSA 1.8
aneuploid cells
now continuous Lupron

Posted 7/1/2012 5:16 AM (GMT 0)
Welcome to HW....

I don't have answers for most of your questions, but my suggestion would be that your husband see a medical oncologist as soon as possible.

It's been my understanding that when attempting surgery, if there are obvious positive lymph nodes, that the surgery be aborted. That information was told to us by a prostate specialty oncologist and there is documentation on the web which basically states the same thing.

Personally, I would be more concerned about what got left behind than I would be about his current PSA of 1.8.

It's quite possible that he may need salvage radiation therapy. A medical oncologist will access the situation and point you guys in the right direction.

Wishing you both the very best.
Posted 7/1/2012 7:48 AM (GMT 0)
Hi pilgrimess, I am a bit surprised that the surgery was done in his case. Some surgeons would have refused to operate in your husband´s case, but ok, that is behind you now, if he is dealing well with the side-effects, no problems. I have been reading about PC for the last 2 years now, and if I were in the US, I would take my husband to see either Dr. Mark Scholz or Dr. Charles Myers or Dr. Eugene Kwon, as they are on top of their science and specialize in treating advanced and difficult cases. Your husband is in early HT and things are fine for now. If his PSA would start to rise, there are new, exciting scanning methods (for example C-11 Choline PET) that can show where cancer cells are that can then be treated successfully with radiation or resection. The whole premise of this approach is that PC is not automatically a systemic disease, but instead follows a step-wise method of spread, and can be caught and treated even in T4 stage. These doctors above (there may be more, but these names I have been more impressed by) are willing to bend the rules, design an individual treatment and are really artists in their field, more so than strictly following protocols which is what most urologists do (can´t blame them for that, though).

My piece of advice is to be very aggressive about the treatment of your husband´s cancer because you have a chance of beating it completely. You can still keep your urologist, but go for a second opinion to a medical oncologist that specializes in treating advanced PC. There are much worse cases than your husband´s and they are still doing well after many years. All the best to you both.
Posted 7/2/2012 10:02 AM (GMT 0)
Welcome Pilgrimess,
If I am reading you correctly his PSA dropped with hormone therapy from 78 down to 1.8 while he still had his prostate. That would seem to me to be a pretty good initial response to the therapy. It will be very interesting to see what the PSA is at the 3 months post surgery mark. It could well hit the "undetectable" mark.
Best wishes,
Bill
Posted 7/2/2012 4:51 PM (GMT 0)
Hi Pilgrimess. You sound like you are becoming really well-informed. Great thing you are doing for your husband. I agree wholeheartedly with Ms. Worry Wart. Your husband should see a medical oncologist with specialized expertise in prostate cancer. The next steps will be really important and you want the best advice you can get. Special Lady mentioned some well-regarded docs. There are a number of others too. If you tell us where you are located, someone here can recommend an oncologist wtih prostate cancer expertise. Best wishes, medved.
Posted 7/2/2012 6:57 PM (GMT 0)
Pilgrimess,

I found an interesting discussion of aneuploidy, S-phase and prostate cancer. Below is the full text, but I'm giving the link as well

Best of luck to you and your husband.

Nellie

www.specialtylabs.com/clients/gbmc/books/display.asp?id=512

GBMC, as testing company said...
DNA Ploidy

In prostate cancer the frequency of DNA aneuploidy increases with grade and stage; whereas, normal and hyperplastic prostate tissue are always DNA diploid. DNA tetraploidy usually indicates prostate carcinoma, but can be found in acute prostatitis and normal seminal vesicle tissue.1 DNA ploidy status correlates with the final histological diagnosis of the prostatectomy specimen and can aid in the diagnosis of prostate carcinoma from prostate core-needle biopsies with a sensitivity of 87% and specificity of 74%.1

Almost one-third of moderately or well-differentiated tumors (Gleason grade 6 or less) are DNA diploid, almost two-thirds are DNA tetraploid and <5% are DNA aneuploid. Among poorly differentiated tumors (Gleason grade 7-10), 66-70% are DNA aneuploid and as many as 21% are DNA multiploid (contain several tumor clones with different DNA indices). The frequency of DNA aneuploidy or DNA tetraploidy increases from 20% in stage A tumors (confined to the prostate) to 58-98% in stage D (metastatic disease).2,3 In core-needle biopsies, the Gleason grade may not always reflect the grade accurately because of the difficulty in identifying the infiltrating pattern in narrow tissue fragments; therefore, the DNA content can be more useful in predicting prognosis.4

Progression in stage A and B prostate carcinoma correlates with stage, pattern of infiltration and ploidy status. In stage A prostate cancer, only 9% of stage A1 (focal) lesions progress compared to 36% of stage A2 (diffuse) lesions. If DNA ploidy is added to stage, the predictive value for progression improves: 67% of DNA aneuploid A2 carcinoma progress; whereas, none of the DNA diploid A1 tumors progress.5 DNA aneuploidy is superior to grade, capsular involvement, number of loci and tumor volume in predicting the failure of radical prostatectomy to eradicate disease (p <0.0004).6 In stage B prostate cancer, all (100%) of the DNA aneuploid tumors progress, but only 15% of patients with DNA diploid prostate carcinoma have tumors that progress.7 In stage A and B prostate carcinoma, progression is seen in all patients with DNA aneuploid tumors, but only 42% of DNA diploid tumors progress.

Patients with stage C DNA diploid tumors have an 85% likelihood of remaining free of disease for 60 months, compared to only 9% for similar patients with DNA aneuploid tumors.8 Patients with low-grade, stage C, DNA diploid tumors have a progression-free survival of 92% at 10 years, compared to 57% for patients with low-grade, stage C non-diploid tumors.9 Disease rarely, if ever, progresses in patients with stage D1, DNA diploid prostate carcinoma who undergo orchiectomy.10 DNA aneuploidy confers a relative risk of 2.3 times of developing recurrent disease than DNA diploid.11 DNA aneuploid core biopsies in patients with prostate cancer metastatic to lymph nodes predicts an earlier time to progression.12 In patients treated with external beam radiation, 89% with DNA content >1.5 progress at 10 years; whereas, 36% of tumors with DNA content <1.5 progress.13 In stage D disease patients treated with anti-androgen therapy, DNA diploid tumors are strongly associated with a favorable response to therapy as determined by lack of progression and survival.14

Non-aneuploid (DNA diploid, near-diploid and tetraploid) stage D1 patients have a lower rate of progression when treated with androgen ablation therapy compared to those with DNA aneuploid tumors. The 4-year disease progression rates for non-aneuploid and aneuploid tumors are 14% and 48%, respectively, and the overall survival rates are 100% and 61%, respectively.15 This difference is not significant when biochemical progression rates (rising PSA) are compared.15

In patients treated with primary hormonal therapy, those with a high S-phase fraction ([SPF] >12%) are less likely to respond than those with a low SPF fraction (0% versus 51%, respectively).16 DNA content measurements could play a role in treatment regimens, particularly because of the poor response to anti-androgen therapy by DNA aneuploid tumors.17

In general, DNA non-aneuploid prostate carcinoma has a better prognosis compared to DNA aneuploid tumors; however, several papers fail to demonstrate significant differences in patient prognosis between DNA non-aneuploid and DNA aneuploid tumors.18-20


Relevant Tests Offered by GBMC
Tests are subject to change. For additional information on these tests or to place an order, please call GBMC Laboratory Customer Services at 410-828-3214.

REFERENCES

Lo J, Kerns B-J, Amling CL, Robertson CN, Layfield LJ. Correlation of DNA ploidy and histologic diagnosis from prostate core-needle biopsies: Is DNA ploid more sensitive than histology for the diagnosis of carcinoma in small specimens? J Surg Oncol 1996:63:41-45.
Aziz DC, Peter JB. DNA ploidy and cell-cycle analysis: tools for assessment of cancer prognosis. J Clin Lab Anal 1991;5:422-38.
Badalament RA, O'Toole RV, Young DC, Drago JR. DNA ploidy and prostate-specific antigen as prognostic factors in clinically resectable prostate cancer. Cancer 1991;67:3014-23.
Humphrey PA, Walther PJ. Adenocarcinoma of the prostate. Part II. Tissue prognosticators. Am J Clin Pathol 1993;100:256-69.
McIntire TL, Murphy WM, Coon JS, et al. The prognostic value of DNA ploidy combined with histologic substaging for incidental carcinoma of the prostate gland. Am J Clin Pathol 1988;89:370-3.
Blute ML, Nativ O, Zincke H, Farrow GM, Therneau T, Lieber MM. Pattern of failure after radical retropubic prostatectomy for clinical and pathologically localized adenocarcinoma: significance of nuclear DNA ploidy patterns studied by flow cytometry. Mayo Clin Proc 1988;63:103-12.
Montgomery BT, Nativ O, Blute ML, et al. Stage B prostate adenocarcinoma. Flow cytometric nuclear DNA ploidy analysis. Arch Surg 1990;125:327-31.
Lee SE, Currin SM, Paulson DF, Walther PJ. Flow cytometric determination of ploidy in prostatic adenocarcinoma of the prostate: influence of tumor deoxyribonucleic acid ploidy. J Urol 1989;142:1262-5.
Nativ O, Winkler HZ, Raz Y, et al. Stage C prostatic adenocarcinoma: flow cytometric nuclear DNA ploidy analysis. Mayo Clin Proc 1989;64:911-9.
Zincke H. Extended experience with surgical treatment of stage D1 adeno<–carcinoma of prostate. Significant influences of immediate adjuvant hormonal treatment (orchiectomy) on outcome. Urology 1989;33(Suppl 5):27-36.
Di Silverio F, D'Eramo G, Buscarini M, Sciarra A, et al. Eur Urol 1996;30:316-321.
van den Ouden D, Tribukait B, Blom JHM, et al. Deoxyribonucleic acid ploidy of core biopsies and metastatic lymph nodes of prostate cancer patients: impact on time to progression. J Urol 1993;150:400-6.
Song J, Cheng WS, Cupps RE, Earle JD, Farrow GM, Lieber MM. Nuclear deoxyribonucleic acid content measured by static cytometry: important prognostic association for patients with clinically localized prostate carcinoma treated by external beam radiotherapy. J Urol 1992;147:794-7.
Zincke H, Bergstralh EJ, Larson-Keller JJ, et al. Stage D1 prostate cancer treated by radical prostatectomy and adjuvant hormonal treatment. Evidence for favorable survival in patients with DNA diploid tumors. Cancer 1992;70:(1 Suppl)311-23.
Pollack A, Troncoso P, Zagars GK, von Eschenbach AC, et al. The Prostate 1997;31:21-28.
Visakorpi T, Kallioniemi O-P, ParonJn IYI, Isola JJ, Keikkinen AI, Koivula TA. Flow cytometric analysis of DNA ploidy and S-phase fraction from prostatic carcinomas: implications for prognosis and response to endocrine therapy. Br J Cancer 1991;64:578-82.
Shankey TV, Kallioniemi O-P, Koslowski JM, et al. Consensus review of the clinical utility of DNA content cytometry in prostate cancer. Cytometry 1993;14:497-500.
Jorgensen T, Yogesan K, Skjorten F, Berner A, Tveter KJ, Danielsen HE, Br J Cancer 1995;71:1055-1060.
Berner A, Waere H, Neslan JM, Paus E, Danelsen HE, Fossa SD. Br J Urol 1995;75:26-32.
Coetzee LJ, Layfield LJ, Hars B, Paulson DF. J Urol 1997157:214-218.

Posted 7/3/2012 11:50 AM (GMT 0)
One more reference, this from the well-respected Bostwick Labs.

An expert medical oncologist specializing in prostate cancer would be able to shed more light, and give your husband the most advanced and promising treatments.

Nellie



/www.bostwicklaboratories.com/global/physicians/medical-library/articles/prognostic-markers.aspx

Bostwick said...
DNA Ploidy

DNA ploidy analysis by digital image analysis is usually performed in routinely processed tissue sections stained by the Feulgen method. The Feulgen stain stoichiometrically binds to hydrolyzed nucleic acids, coloring nuclei blue according to the amount of DNA present (1-3). A good correlation exists between DNA ploidy and cancer histologic grade, and DNA ploidy adds clinically useful predictive information for some cancer patients (1-3). DNA ploidy analysis of prostate cancer provides important predictive information which supplements histopathologic examination. Patients with diploid tumors have a more favorable outcome than those with aneuploid tumors. Among patients with lymph node metastases treated with radical prostatectomy and androgen deprivation therapy, those with diploid tumors may survive 20 years or more, whereas those with aneuploid tumors may die within 5 years (4). DNA ploidy analysis of needle biopsies is prognostically useful, particularly when combined with the proliferative fraction (5).

Proliferating cell nuclear antigen (PCNA)

Proliferating cell nuclear antigen (PCNA) is an auxiliary protein for DNA polymerase which reaches maximal expression during the S phase of the cell cycle (6). Hence, PCNA has been widely used as an index of the proliferative activity of cancers. The PCNA labelling index is reported to be lowest in benign normal prostatic epithelium and organ-confined cancer but to increase progressively from well- through poorly-differentiated invasive prostate cancer, although there is wide variance (7). The correlation of PCNA index is strong with cancer stage (6-8). Hence, high PCNA labelling indices may indicate progression of prostate cancer (9-10), and may be an independent prognostic indicator (9).

Ki-67 and MIB-1

The Ki-67 antibody recognizes a nuclear antigen present in proliferating cells, but absent is resting cells (11). Since the original antibodies to Ki-67 exhibited only poor immunoreactivity in fixed paraffin-embedded tissues, the MIB-1 antibody was developed against recombinant parts of the Ki-67 antigen for specific use on formalin-fixed and paraffin wax-embedded tissues (11). In prostate cancer, a high proliferation index for either antibody appears to addlittle predictive information for patient outcome above the traditional indicators of Gleason score, pathologic stage, and DNA ploidy (12-14). However, the Ki-67 labelling index may discriminate between organ confined and metastatic cancer (14). Hence, elevation in the proliferation indices of Ki-67/MIB-1 appear to reflect progression (15, 16). This is further reflected in an association between expression of Ki-67 and the epidermal growth factor receptor (17), mutant p53 (18, 19), particular chromosomal aberrations (20), and perineural invasion (21). Taken together, all of these findings suggest that Ki-67 expression may be a weak prognostic indicator of recurrence (22, 23), progression (16, 24) and survival (19, 23, 25).

Posted 7/3/2012 8:14 PM (GMT 0)
Nellie, thanks for the education.

In case others are curious about DNA ploidy, Wikipedia has a pretty good treatment of it http://en.wikipedia.org/wiki/Ploidy.
Summarizing from the description, "normal" (non-sex) human cells are diploid, meaning that they have 2x the proper base integer number, or 2x13. Aneuploid cells do not follow this normal convention, and are abnormal as a result. Some chromosomal abnormalities we are all familiar with: the extra chromosome in Down Syndrome, for example, is aneuploidy. The article claims that DNA aneuploid tumors, rather than diploid tumors, have a less favorable outcome.

This shows how the advances in genetics are helping us determine aggressiveness in tumors - this next decade is going to be interesting.
Jeff
Posted 7/5/2012 12:29 PM (GMT 0)

Thanks to all who have responded. We are at one of the leading cancer centers and have real confidence in his doctor/team. His first post-surgery PSA test is in a month, so we are hoping for good news there.

Pilgrimess

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